BGU researchers are developing a novel therapeutic strategy for treating Inflammatory Bowel Diseases (IBD) by sequestering inflammation-inducing molecules secreted by gut bacteria. The method, invented by Prof. Ehud Ohana (pictured below) from BGU’s Department of Clinical Biochemistry and Pharmacology, is based on findings from Prof. Ohana’s lab showing that gut levels of succinate, a metabolic molecule involved in various biochemical processes in living cells, were markedly increased in IBD, corresponding to changes in succinate-metabolizing gut bacteria. Several recent studies show that succinate acts as a pro-inflammatory metabolite, in particular driving inflammatory activity of macrophages.

Inflammatory bowel diseases (IBD), primarily including Crohn’s disease and ulcerative colitis, affect up to 1.5% of US adults and millions of people globally and lead to a severely impaired quality of life and significant morbidity. If remained untreated, IBD patients are at high risk for developing colon cancer. Currently, there is no cure for IBD, and treatments revolve around various methods for controlling inflammation by reducing the activity of the immune system. In severe cases, surgical intervention is required.

The findings were published in Cell Reports​ in a paper titled “A transepithelial pathway delivers succinate to macrophages thus perpetuating their pro-inflammatory metabolic state“. This study was conducted by Moran Fremder, a graduate student in Prof. Ohana’s lab (in the MD/Ph.D. program) and in collaboration with Prof. Jae Hee Cheon from Yonsei UniversitySeoul, South Korea.

The novel method targets and chelates excess succinate in IBD patients to attenuate its absorption, by using peptide sequences that mimic the succinate binding site in succinate binding enzymes. In parallel, biochemical methods will be used to measure succinate concentrations in biological specimens for a better diagnosis and content monitoring of IBD and related extra-intestinal symptoms. These technologies will be used as a companion tool to diagnose and treat IBD.

“Current treatments for IBD include antibiotics, steroids, and biological treatments aimed at inhibiting the activity of the immune system. Such treatments can have long-term side effects, and none address the root causes underlying IBD which are largely unknown,” explained Prof. Ohana. “Our novel findings show that IBD is driven, at least partially, by changes in the activity of gut bacteria and by the accumulation of succinate in the gut, leading to chronic inflammation. Therefore, chelation of succinate can treat IBD and reduce inflammation. Furthermore, our therapeutic peptides are identical to molecules that naturally exist in our body and are therefore unlikely to provoke a harmful immune reaction.”

“This promising therapeutic approach developed by researchers at BGU is like that of diabetes treatment, wherein blood sugar levels are constantly monitored and adjusted using medication. It is, therefore, more dynamic and personalized than existing medications and is likely to significantly improve the quality of life of people suffering from IBD,” added Josh Peleg, CEO, BGN Technologies. “We have filed for patent protection and are now seeking a strategic partner for the further developing and commercializing this promising invention.”